Water quality modeling is an important issue for both engineers and scientists. The QUAL2K model is a simulation tool that has been used widely for this purpose. Uncertainty and sensitivity analysis is a major step in water quality modeling. This article reports application of Monte Carlo analysis and classification tree sensitivity analysis in the modeling of the Zayandehrood River. First the model was calibrated and validated using two sets of data. Then, three input values (stream flow, roughness and decay rate) were considered for both analyses. The Monte Carlo analysis was conducted using triangular distribution of probability of occurrence for the input parameters. The classification tree analysis classifies outcome values into non-numeric categories. Considering the relationships between the input parameters in the classification tree analysis is the most important advantage of it. The analyses demonstrated the key input variables for three points of the river. The dissolved oxygen levels were mainly sensitive to the decay rate coefficient along the river.